Division of Oncological Sciences, Cancer Early Detection Advanced Research Center, Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon.
Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Cancer Res. 2022 Aug 16;82(16):2824-2825. doi: 10.1158/0008-5472.CAN-22-2065.
Activation of p53 regulates a transcriptional program that can cause cell cycle arrest, senescence, apoptosis, and ferroptosis, which are potent tumor suppressive mechanisms. Unexpectedly, Makino and colleagues show in this issue of Cancer Research that the constitutive activation of p53 in murine hepatocytes leads to tumor development. Detailed analyses indicate that p53 activation leads to loss of hepatocytes, increased expression of chemokines and humoral factors, and expansion of the hepatic progenitor cell population. These progenitor cells are highly proliferative, show chromosomal instability, and eventually transform. In chronic liver disease in humans, activation of p53 is associated with increased liver cancer development. This study highlights the complexity and non-cell autonomous nature of the physiologic p53 response. See related article by Makino et al., p. 2860.
p53 的激活调节了一个转录程序，该程序可导致细胞周期停滞、衰老、细胞凋亡和铁死亡，这些都是强有力的肿瘤抑制机制。出人意料的是，Makino 及其同事在本期《Cancer Research》中表明，p53 在小鼠肝细胞中的组成性激活会导致肿瘤的发生。详细分析表明，p53 的激活导致肝细胞的丧失、趋化因子和体液因子表达的增加以及肝祖细胞群体的扩增。这些祖细胞具有高度的增殖能力，表现出染色体不稳定性，最终转化。在人类慢性肝病中，p53 的激活与肝癌的发展增加有关。这项研究强调了生理 p53 反应的复杂性和非细胞自主性质。见 Makino 等人的相关文章，第 2860 页。
